Diagnostic accuracy of the neurological upper limb examination II: Relation to symptoms of patterns of findings

Background: In a sample of patients in clinical occupational medicine we have demonstrated that an upper limb neurological examination can reliably identify patterns of findings suggesting upper limb focal neuropathies. This further study aimed at approaching the diagnostic accuracy of the examination. Methods: 82 limbs were semi-quantitatively assessed by two blinded examiners ( strength in 14 individual muscles, sensibility in 7 homonymous territories, and mechanosensitivity at 10 locations along nerves). Based on the topography of nerves and their muscular and sensory innervation we defined 10 neurological patterns each suggesting a localized nerve affliction. Information on complaints ( pain, weakness and/or numbness/tingling) collected by others served as a reference for comparison. The relation between the presence of pattern(s) and complaints was assessed by kappa-statistics. Sensitivity, specificity, and positive/negative predictive values were calculated, and pretest odds were compared to post-test probability. Results: The two examiners identified pattern( s) suggesting focal neuropathy in 34/36 out of 38 symptomatic limbs, respectively (kappa = 0.70/0.75), with agreement in 28 limbs. Out of 44 non-symptomatic limbs the examiners agreed on absence of any pattern in 38 limbs. With concordance between the examiners with regard to the presence or absence of any pattern, the sensitivity, specificity, positive and negative predictive values were 0.73, 0.86, 0.93 and 0.90, respectively. While the pre-test odds for a limb to be symptomatic amounted to 0.46 the post-test probability was 0.81. For each examiner the post-test probability was 0.87 and 0.88, respectively. Conclusion: The improved diagnostic confidence is an indication of one aspect of construct validity of the physical examination. For determination of clinical feasibility of the examination further studies are required, most importantly 1) studies of validity by means of comparison with additional references and 2) studies of the potential benefit that can be attained from its use

Anti-citrullinated protein antibodies cause arthritis by cross-reactivity to joint cartilage

Today, it is known that autoimmune diseases start a long time before clinical symptoms appear. Anti-citrullinated protein antibodies (ACPAs) appear many years before the clinical onset of rheumatoid arthritis (RA). However, it is still unclear if and how ACPAs are arthritogenic. To better understand the molecular basis of pathogenicity of ACPAs, we investigated autoantibodies reactive against the C1 epitope of collagen type II (CII) and its citrullinated variants. We found that these antibodies are commonly occurring in RA. A mAb (ACC1) against citrullinated C1 was found to cross-react with several noncitrullinated epitopes on native CII, causing proteoglycan depletion of cartilage and severe arthritis in mice. Structural studies by X-ray crystallography showed that such recognition is governed by a shared structural motif "RG-TG" within all the epitopes, including electrostatic potential-controlled citrulline specificity. Overall, we have demonstrated a molecular mechanism that explains how ACPAs trigger arthritis

Value of hospital antimicrobial stewardship programs [ASPs]:a systematic review

Abstract Background Hospital antimicrobial stewardship programs (ASPs) aim to promote judicious use of antimicrobials to combat antimicrobial resistance. For ASPs to be developed, adopted, and implemented, an economic value assessment is essential. Few studies demonstrate the cost-effectiveness of ASPs. This systematic review aimed to evaluate the economic and clinical impact of ASPs. Methods An update to the Dik et al. systematic review (2000–2014) was conducted on EMBASE and Medline using PRISMA guidelines. The updated search was limited to primary research studies in English (30 September 2014–31 December 2017) that evaluated patient and/or economic outcomes after implementation of hospital ASPs including length of stay (LOS), antimicrobial use, and total (including operational and implementation) costs. Results One hundred forty-six studies meeting inclusion criteria were included. The majority of these studies were conducted within the last 5 years in North America (49%), Europe (25%), and Asia (14%), with few studies conducted in Africa (3%), South America (3%), and Australia (3%). Most studies were conducted in hospitals with 500–1000 beds and evaluated LOS and change in antibiotic expenditure, the majority of which showed a decrease in LOS (85%) and antibiotic expenditure (92%). The mean cost-savings varied by hospital size and region after implementation of ASPs. Average cost savings in US studies were $732 per patient (range:$2.50 to $2640), with similar trends exhibited in European studies. The key driver of cost savings was from reduction in LOS. Savings were higher among hospitals with comprehensive ASPs which included therapy review and antibiotic restrictions. Conclusions Our data indicates that hospital ASPs have significant value with beneficial clinical and economic impacts. More robust published data is required in terms of implementation, LOS, and overall costs so that decision-makers can make a stronger case for investing in ASPs, considering competing priorities. Such data on ASPs in lower- and middle-income countries is limited and requires urgent attention